Experimental animal models resembling rheumatoid arthritis

Abstract

The experimental animal models of arthritis which in certain aspects share similarities to human rheumatoid arthritis are reviewed. Various methods have been applied to induce in animals experimental models of arthritis which would provide important insights into the aetiopathogenetic mechanisms of human RA. Immunological methods and infectious agents induced the most interesting models. The histology of the synovial tissue, regardless of the inducing mechanisms, is similar to the lesions of RA. Yet, none of these experimental models of arthritis reflects all the articular and systemic features, the immunological profile and the genetic factors which characterize the human disease. The animal models of arthritis reported here and the development of new ones may ultimately offer the information necessary for the understanding of the mechanisms involved in the aetiopathogenesis of human rheumatoid disease.

Protection against collagen-induced arthritis by intramuscular gene therapy with an expression plasmid for the interleukin-1 receptor antagonist

“…These data indicated that CIA mice display marked upregulation of IL-1b in joints accompanied by synovial growth similar to human RA. 1,2,4 Intramuscular gene therapy using IL-1Ra DNA inhibits CIA in mice As a plasmid expression vector for intramuscular gene therapy, we used pCK, which has been shown to drive a high level of gene expression in the skeletal and cardiac muscles of mice. 22,23 The human IL-1Ra coding sequence was cloned to pCK, resulting in pCK-IL-1Ra (Figure 2a).…”

“…1 Although the causes of RA are not fully understood, various experimental and clinical studies suggest that proinflammatory cytokines, particularly interleukin-1 (IL-1) among others, have an important role in RA pathogenesis. [2][3][4][5] The IL-1 receptor antagonist (IL-1Ra) is a natural protein that competitively inhibits the binding of IL-1b and IL-1a to IL-1 receptor types I and II in humans and various animals, and improves the inflammatory symptoms of arthritis in experimental animal models.…”

“…[2][3][4][5] The IL-1 receptor antagonist (IL-1Ra) is a natural protein that competitively inhibits the binding of IL-1b and IL-1a to IL-1 receptor types I and II in humans and various animals, and improves the inflammatory symptoms of arthritis in experimental animal models. 1,[6][7][8][9][10] Several independent clinical trials have been completed in which the recombinant IL-1Ra protein has been administered for a long-term period to patients with RA. 11,12 The results indicate that treatment with IL-1Ra lowers the levels of proteins involved in the acute phase of RA and the counts of swollen joints and, furthermore, may inhibit radiographic progression of the disease.…”

Electro-gene therapy of collagen-induced arthritis by using an expression plasmid for the soluble p75 tumor necrosis factor receptor-Fc fusion protein

“…1 Although the causes of RA are not fully understood, various experimental and clinical studies suggest that proinflammatory cytokines, particularly tumor necrosis factor-a (TNF-a), play an important role in RA pathogenesis. [2][3][4][5][6] TNF concentrations are increased in the synovial fluid of persons with active RA 7,8 and increased plasma levels of TNF are associated with joint pain.…”

Multiple Recombinant Adeno-Associated Viral Vector Serotypes Display PersistentIn VivoGene Expression in Vector-Transduced Rat Stifle Joints

“…Although CD90 + synovial fibroblasts are highly vulnerable to genetic modification, this cell population is also transient, with an apparent half-life in normal joints of less than 1 month (Gouze et al, 2007). This half-life decreases further in diseased joints (Remmers et al, 1990;Kaklamanis, 1992;Pan et al, 1999). If the majority of vector-transduced cells in a target joint are transient, the long-term therapeutic effects in the joint will be based on the small remaining nontransient cell population.…”